Clinical measures of heparin's effect and thrombin inhibitor levels in pediatric patients with congenital heart disease.

In this investigation, we examined the relationship among three thrombin inhibitors, antithrombin III (ATIII), heparin cofactor II (HCII), and alpha-2-macroglobulin (alpha2M), and several clinical tests of heparin's effect in pediatric patients with congenital heart disease undergoing cardiopulmonary bypass. One hundred eighteen children were stratified into six age groups: <1 mo, 1-3 mo, 3-6 mo, 6-12 mo, 12-24 mo, and >10 yr. Baseline ATIII, HCII, and alpha2M values were measured. Baseline celite- and kaolin-activated clotting times (ACT) were also measured and repeated 3 min after a standard heparin dose of 400 U/kg. Differences in ACT values before and after heparin administration and a heparin dose-response relationship were calculated for each patient. Kaolin-activated ACT tests showed less variation after heparin administration than celite-activated tests. In contrast to what has been demonstrated in adults, ATIII showed no positive correlation with the clinical tests of heparin's effect nor did the other thrombin inhibitors. Additionally, patients <1 mo old had unexpectedly low levels of alpha2M accompanying their expected low levels of ATIII and HCII. Our findings raise concerns about the ability of heparin to adequately anticoagulate these neonates during cardiopulmonary bypass and, consequently, challenge the accuracy of ACT prolongation to truly reflect the extent of their anticoagulation.

Fibrinogen in children undergoing cardiac surgery: is it effective?

There is speculation based on laboratory tests and biochemical data regarding the functional integrity of the fibrinogen in young children. Recent investigations in adults have demonstrated that their fibrinogen level correlates with the thromboelastogram maximum amplitude (MA) after modification with a glycoprotein IIb/IIIa receptor blocker that uncouples platelet-fibrinogen interactions. We postulate that if the fibrinogen of young children is functionally intact then their fibrinogen levels should also correlate with modified thromboelastogram MA values as they do in adults. We compared modified and unmodified thromboelastogram variables of 250 children <2 yr old undergoing cardiac surgery with their fibrinogen levels and platelet counts. Five age groups were distinguished to determine if and when correlations become significant (<1 mo, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo). Fibrinogen levels correlated with modified thromboelastogram MAs only in the 12-24 mo group. In this 12-24 mo age group other correlations between fibrinogen levels and thromboelastogram variables influenced by fibrinogen also became significant, as did correlations noted in adults between platelet counts and thromboelastogram variables. We conclude that the fibrinogen of children <12 mo old with congenital heart disease is qualitatively dysfunctional.

The effect of insufflation pressure on pulmonary mechanics in infants during laparoscopic surgical procedures.

BACKGROUND: Few studies have reported objective measurements of pulmonary changes under controlled conditions in infants undergoing laparoscopic procedures. We objectively measured the pulmonary effects of laparoscopically-induced pneumoperitoneum in infants less than 1 year of age undergoing surgical procedures under general anaesthesia. METHODS: Nineteen ASA I-II patients less than 1 year of age were enrolled in this direct observational study. Anaesthetic technique included inhalation induction using sevoflurane/O2/air and neuromuscular blockade. Infants were ventilated using 10-15 ml.kg-1 tidal volume at a respiratory rate sufficient to achieve normocarbia [PECO2 4.6-5.8 kPa (35-45 mmHg)]. Opioids and regional anaesthesia techniques were used when appropriate. Peak inspiratory pressure (PIP), expiratory tidal volume (Vt), endtidal carbon dioxide concentration (PECO2) and dynamic compliance (COMPdyn) were recorded at baseline, 5, 10 mmHg and maximal insufflation pressure (Pmax). Pmax was limited to 12 mmHg for infants <5 kg, 15 mmHg for infants >5 kg. At steady state Pmax, ventilator changes were implemented to restore Vt and PECO2 to within 10% of baseline. Each patient served as his own control. RESULTS: At Pmax, average PIP increased 18%, average Vt decreased 33%, average PECO2 concentration increased 13%, average COMPdyn decreased 48%; O2 saturation fell in 41% of patients. Twenty ventilator adjustments were required; one patient experienced no changes in measured pulmonary mechanics, requiring no ventilator changes. CONCLUSIONS: Pulmonary mechanics in infants change significantly during laparoscopic CO2 pneumoperitoneum; the magnitude of change correlates directly with intraperitoneal pressure. Greater than 90% of infants required at least one ventilatory intervention to restore baseline Vt and PECO2.

Midazolam premedication in children: a comparison of two oral dosage formulations on sedation score and plasma midazolam levels.

We compared two available oral formulations of midazolam with respect to sedation score and plasma midazolam levels in pediatric surgical patients 2-10 yr old. The commercially available oral syrup was compared with a mixture of the IV midazolam preparation in Syrpalta syrup at an equivalent concentration of 2 mg/mL. ASA status I-II patients were randomly assigned to receive 0.5 mg/kg of either the commercial syrup (Group 1) or the prepared mixture (Group 2) as anesthetic premedication. Observer's Assessment of Alertness/Sedation scores were obtained by a blinded observer at 15 and 30 min after drug administration. Plasma midazolam levels were acquired exactly 45, 60, and 90 min after administration. Group 2 patients had a significantly lower median Observer's Assessment of Alertness/Sedation score (Group 1, 17; Group 2, 15) at 30 min (P < 0.03) and significantly higher mean plasma midazolam levels at all three acquisition times (mean +/- SD) (45 min: 63.1 +/- 23.9 ng/mL, Group 2; 43.4 +/- 19.6 ng/mL, Group 1; 60 min: 45.8 +/- 18.2 ng/mL, Group 2; 30.8 +/- 17.9 ng/mL, Group 1; 90 min: 28.9 +/- 12.6 ng/mL, Group 2; 21.0 +/- 8.9 ng/mL, Group 1) (P < 0.02). We conclude that IV midazolam mixed in Syrpalta syrup yields more reliable sedation and correspondingly higher plasma levels than an equivalent dose of the commercially formulated and marketed preparation.

Oral midazolam premedication in preadolescents and adolescents.

UNLABELLED: We sought to determine the influence of preoperative oral midazolam on 1) sedation score, 2) measures of anesthetic emergence, 3) recovery times, and 4) bispectral index (BIS) measurements during sevoflurane/N(2)O anesthesia in adolescent patients. Fifty ASA I and II patients 10-18 yr of age were enrolled in a prospective double-blinded study. Patients were randomized to receive either 20 mg of midazolam (M group) or midazolam vehicle (P group) as premedication. Before the induction, sedation scores and BIS values were determined in all patients. After inhaled induction and intubation, expired sevoflurane was stabilized at 3% in 60% N(2)O and the corresponding BIS (BIS I) recorded. Upon completion of surgery, sevoflurane was stabilized at 0.5% and the BIS (BIS E) again recorded. Plasma midazolam levels were measured at the time of BIS I and BIS E. There were no significant differences between groups in awakening time, sevoflurane/N(2)O awakening concentrations, time to postanesthesia care unit discharge, or BIS I and BIS E measurements. Sedation scores and preinduction BIS values were significantly lower in Group M than in Group P, although only 40% of midazolam-treated patients exhibited detectable sedation, with marked interindividual variability in achieved plasma midazolam levels. Detectable preoperative sedation was predictive of delayed emergence. IMPLICATIONS: We demonstrated a measurable sedative effect of oral midazolam in adolescents which correlated with simultaneous bispectral index (BIS) measurement. Considering the overall group, midazolam premedication did not affect intraoperative BIS, emergence times, or recovery times compared with placebo controls. Detectable preoperative sedation, and not merely midazolam administration, was predictive of prolonged emergence.